Flashcards in Inherited Immunodeficiencies Deck (89):
What is asplenia ?
A genetic or acquired deficiency that renders the spleen inactive. This will place you at a high risk for infection by encapsulated bacteria and septic infections. The spleen is a blood filter and macrophages take up pathogens from the blood.
How can you acquire asplenia ?
Have your spleen removed after a traumatic injury.
How do you treat your patients that have asplenia ?
Give them prophalactic antibiotics when performing any procedure (even dental work) and vaccinate them against capsulated bacteria.
What will a phagocyte defect result in ?
It will result in a defect in the recruitment of phagocytes to the sites of extravascular infection and will result in severe immunodeficiency. This is a process that is mediated by cell surface adhesion molecules.
What is CD-18 deficiency ?
Leukocyte adhesion deficiency which will result in defective migration into infected tissues.
What happens in chronic granulamatous disease?
Phagocytes cannot produce reactive oxygen species resulting in an impaired ability to kill bacteria (autosomal recessive ) Patients with this condition will have chronic bacterial infections.
What is myloperoxidase deficiency ?
In this condition the patients macrophages are unable to efficiently kill phagocytosed microbes because they have impaired ability to produce hypochlorus acid and toxic oxygen species and therefore will have an impaired respiratory burst.
What is chediak - Higashi syndrome ?
Partial albinism abnormal platelet function and severe immunodeficency
What are neutropenias ?
Neutropenias are characterized by low numbers of granulocytes usually defined as a neutrophil count below 500 cells / uL /
Describe severe congenital neutropenia
Characterized by low numbers of granulocytes usually defined as neutrophil could less than 500 cells/uL.
What is Kostmann syndrome ?
Severe congenital neutropenia. This is an autosomal recessive condition that is associated with a gene abnormality of granulocyte colony stimulating factor.
What is a common name for ( X-Linked Hypohydrotic ectodermal dysplasia and immunodeficiency) and what does it do ?
NEMO (I love that Fiiish- entourage quote) A genetic condition where PRR are intact but transcription of genes that should be expressed after binding are not.
What do toll like receptors stimulate ?
NFkB which controls cytokine and chemokine expression.
How do you treat NEMO ?
2x daily injections of Gamma Globulin
What will a defect in properdin P cause ?
Properdin P enhances the activity of the alternative complement pathway will lead to heightened sensitivity to Niceria
What problems will a patient have that is deficient with C-1 Inhibitor defects?
Patients with C1 inhibitor defects fail to control the inappropriate activation of the classical complement cascade. The uncontrolled cleavege of C2 will result in the production of the C2b vasoactive fragment. This will cause fluid accumulation in tissues and epiglottic swelling that can lead to death
What will happen to patients who lack the decay acceleration factor and CD59 ?
These protect the host cell surfaces against the complement cascade. Without them the complement cascade will degrade the RBC's
What will a defect in C3 cause ?
Susceptibility to encapsulated bacteria. This will show you the emphasis of C3b in opsonization.
What is the main concern with a defect in antibody production ?
Defective antibody production will creat an inability for a cell to clear its self from extracellular pathogens and viruses that are sensitive to neutralizing antibodies.
What will a defect in C5-C9 cause ?
Susceptibility to niceria. You will not be susceptible to every pathogen because you will still be able to opsonize bacteria
What is X-Linked agammaglobulinemia (XLA)
Absence of immunoglobins in the serum. The defective gene codes for a protein tyrosine kinase which is expressed on b cells and neutrophils. The disease will display a profound B cell deficiency making the host susceptible to both extracellular and intracellular pathogens
What will pre-B cell deficiency result in
This is a result of a mutation in the Delta 5 gene. This is a component of the surrogare light chain that paris with the my heavy chain during somatic recombination of light chain genes. This will result in a profound B cell deficiency
What will selective IgA do to the host ?
IgM can be transported across the mucosal epithelium and do the job of IgA. When you have low levels of IgA the body will produce more of the other copies of the other isotype.
What is X-linked Hyper IgM syndrome ?
A disease that is characterized by high levels of IgM but low concentrations of the other isotypes. The most common defect will be that T cells can not interact with CD-40 on T cells.
What will a TAP transporter have a deficiency with ?
This will result in very low levels of MHC class 1 molecules and defective responses to intracellular pathogens due to CD8+ T deficiency
What will a CD-8 alpha chain defect result in ?
This will have the same presentation as the TAP transport defect
Define Severe Combined Immune Deficiency
This is when patients have T cell deficits in both CD4 and CD8 T cells.
What is adenosine deaminase deficiency?
A deficiency in purine nucleotide phosphorylase deficiency. This will result in the SCID phenotype which leads to the accumulation of nucleotide catabolites that are particularly toxic to developing T and B cells
What is bare lymphocyte syndrome
Lack of expression of all MHC II molecules which results in inability of CD4 T cells to be positively selected in the thymus.
What is DiGeorge syndrome ?
This disease results from a small deletion on chromosome 22 that results in congenital heart disease, palatal abnormalities, learning disabilities and hypocalcemia
What is complete digeorge syndrome ?
Liek normal digeorge syndrome but the patients also have an underdeveloped or nonexistent thymus
What is common gamma chain deficiency ?
The common gamma chain is the signaling component of a numner of cytokine receptors. This protein interacts with JAK-3 to initiate signaling once the cytokine receptor has been engaged by tytokine ginding. If you do not produce a functional form of this protein you can not initiate signaling of any of the cytokine receptors.
What is Omenn syndrome?
A mis-sence mutation that result in partially active RAG enzymes. Lack of RAg activity results in an absence of B cells and lower number of oligocolnial auto-reactive T Cells
What is Zap 70 Deficiency ?
A deficiency in Zap-70 which is a tyrosine kinase that associates with phospholipid ITAMS during signaling via the T cell receptor complex. These patients will have abscence of CD8 T cells but normal numbers of CD4 T cells. The result is SCID. This is treated with Bone marrow transplant.
What is AIRE ?
A transcroption factor that regulates expression of several hundred host-tissue specific genes by epithelial cells in the thymic medulla. The host specific proteins sere as a source of self-proteins
What does APECED result from ?
It results from genetic deficiency of a gene that encodes the autoimmune regulator AIRE; this results in development of a myraid of autoimmune responses.
What is IPEX ?
A genetic deficiency of Fox P3 expression in regulatory CD4 T cells. This results in extreme autoimmunity due to lack of T cell regulatory function.
What is ALPS ?
Autoimmune Lymphoproliferative Syndrome. This is characterized by lymphadenopathy and splenomegaly.
What do IPEX patients present with ?
Watery diarrhea, eszematous dermatitis and endocrinopathy type 1
What do ALPS patients present with ?
Autoimmune hemolytic andmia and neutropenia, thrombocytopenia, lymphadenopathy, splenomegaly and also have a large number of CD4- CD8_ cells.
What two critical functions do CD4 cells serve ?
They are important to both antibody mediated and cell mediated immune response.
What will a nonsence mutation in perforin cause ?
It will result in a decreased CTL activity but patients will ahve a normal number of CD8 cells. CTL's are unable to induce programmed cell death of target cells.
What will a defect in IgG2 result in ?
Susceptibility to encapsulated bacteria
What will a deficiency in IgG1 result in ?
Susceptibility to many bacterial and viral pathogens
How can common autoimmunities be treated ?
They can be treated by replacement therapy as well as passive immunization.
What is gene therapy?
Treatment for immunodeficiencie, a functional copy of the defective gene can be introduced into stem cells derived from the patients bone marrow. Once these cells can be genetically realtered they can be reintroduced into the stem cells derived from the patients bone marrow.
What are most immunodeficiencies treated with ?
Most immunodeficiencies are due to defective genes in the hematopoietic stem cells. These conditions can be treated with bone marrow transplantation from a health donor.
What is cord blood ?
Fetal blood that is extracted from the placenta after birth. It can serce as an alternatice source of stem cells for transplantation. This is a nonincasive procedure but the disadvantage is that fewer stem cells are obtained from each chord sample.
What is the major complication from bone marrow transplants ?
Graft Vs Host Disease (GVHD)
What does Cytadine Deaminase do?
Activation induced cytidine deaminase deficiency is required for isotype switching and somatic hypermuation. Without these we will have a build up of a ton of IgM because we can not switch it to any other form of an antibody
What does purine nucleotide phosphorylase do ?
A deficency in Purine Nucleotide Phosphorylase will result in accumulation of toxic catabolites that will kill B cells and T cells
What does the common gamma chain do ?
The common Gamma chain is a signaling component of a number of cytokine receptors (IL2,IL4,IL7,IL9,IL15) and interacts with JAK-3. This impaired signaling results in failure of T cells to proliferate
What does Lambda 5 do ?
Lambda 5 is a component of the surrogate light chain that pairs with the mu heavy chain during somatic recombination of light chain genes. NONFUNCTIONAL surrogate light chain results in the inability of the developing B cells to produce the pre-B cell receptor. They will undergo apoptotic death
What does C40 do ?
Involved in the second signal of B cell activation. Remember
What does a deficiency in G6PD do ?
Defective respiratory burst
Do macrophages have any role in viral infections, explain your answer
No macrophages can not engulf an entire cell. Viruses replicate inside the cell
What is a myeloperoxidase deficiency ?
Patients macrophage are unable to efficiently kill phagocytosed microbes because they hace imparied ability to produce hypochlorous acid and toxic oxygen species and therefore have a defective respiratory burst
IgG2 deficency will put you at risk to ?
Omenn syndrome ...
Lack of RAG-1 and RAG-2
Lack of Zap 70 will cause
Impaired ability for T cells to communicate
Fox P-3 .....
IPEX, and Fox P-3 is responsable for T reg cell function
Chronic Granulamatous disease ...
NADPH Oxidase in phagocytes... they cant produce O-
Deficencies of myeloperoxidase in neutrophil granules and macrophage lysosomes... Impaired production of toxic oxygen species
Deficiency in complement proteins ..
Susceptibility to extracellular bacteria
What normally targets encapsulated bacteria ?
Alternate pathway of the complement system
X-Linked A gamma globulinemia affects ?
Burtons Thymidine Kinase, involved in B cell maturation. Leaves patients with no humoral immune response.
Describe the Ab conc. in convalescent serum
Lower IgM than IgG
What will a CD3 deficiency cause ?
Total lack of T cell function
What happens in Omenn syndrome ?
Mis-scence mutation that result in partially active RAG enzymes. This will result in an absence of B cells and low numbers of self reactive T cells
Autoimmune posyendocrinopathy candididasis ectodermal dystrophy
Defect in AIRE, this transcription factor regulates expression of several hundred host specific genes by wpithelial cells in the thymic medulla. This will break down the negative selection process in T cell development
ALPS what does this cause
Failure of immune cells to indergo apoptotic death following an immune response which causes an overpopulation in the secondary lymph tissues.
Chronic Granulamatous Disease ?
Defective NADPH oxidase in which the phagocytes cannot produce O2- to kill engulfed bacteria
Myeloperoxidase Deficiency ?
Defective Myeloperoxidase in neutrophil Granules and macrophage lysosomes and impaired production of toxic oxygen species. Will result in chronic bacterial and fungal infections
Glucose 6 Phosphate Dehydrogenase
Defective Respiratory Burst
Defective NK cells will lead to a defect in ________ function. Hint you will use this to fight Myobacterium Avium infections
A defect in NFkB will result in what ?
Ineffective cytokine and chemokine signaling
What will NEMO patients present with ?
Unusual skin and blistering and changes in skin color. Deep set eyes, sparce or fine hair, conical or missing teeth. Recurrent bacterial or viral infections.
What is wrong with NEMO patients ?
Without activation of PRR when a foreign invader is there you will not have activation of macrophages and attraction of neutrophils. In a sense you will not have an effective innate immune system
What is Lambda 5
Lambda 5 is a component of the surrogate light chain that pairs with the mu heavy chain during somatic recombination of light chain genes. This will result in developing B cells to not express the pre-B cell receptor and undergo apoptotic death.
What causes bare lymphocyte syndrome
Lack of negative selection of T cells in the thymus
What do ADA and PNP cause
Both result in the SCID phenotype which is the accumulation of toxic metabolites which are toxic to developing T and B cells
What will common gamma chain deficiency result in ?
The common gamma chain reacts with JAK kinase which is engaged by cytokine binding.
What will a deficiency in Fox P3 result in ?
IPEX, which will result in a lack of regulatory T cells and autoimmunity of regulatory T cells
Omenn Syndrome ?
Lack of RAG and the patient will have no B calls and a very small number of self reactive T cells
Why does common gamma chain result in SCID ?
Without the ability of cytokine signaling you will not have the ability of T and B cell maturation
Is hyper IgM syndrome due to common gamma chain ?
No it is due to CD-40 defects which result in the inability of T cells to interact with B cells. In addition T cells cannot activate macrophages.
What else can cause Hyper IgM syndrome
Activation induced cytidine Deaminase will result in the inability of class switching
If you have hyper IgM can you hyperacute rejection of a graft ?
Yes because IgM can activate the complement cascade and respond to the invader.